The Doha Declaration has entrusted to the members of WHO the right to use the compulsory licensing for drug patents in the face of global public health crises.Although the basic compulsory licensing system for drug patents has been established in China, the efficiency of its implementation is low, the responsibility of its executive departments is unclear, the related rules are not fully understood by pharmaceutical enterprises, it is thus necessary to improve and perfect the relevant legal provisions and systems in order to effectively improve the accessibility of drugs.

Comprehensive and designed experiment is beneficial to improving and developing students' comprehensive quality and innovation ability.In the last two years,we have carried out the comprehensive and designed experiment of physiology among the seven-year program students,which combine book knowledge and clinics.It has proved that this teaching mode can not only help students master the knowledge systematically but also lay a good foundation for them to analyze the clinical problems.

OBJECTIVE:To study the relative bioavailability,pharmacokinetics and bioequivalence of domestic nisoldipine tablets in healthy volunteers.METHODS:A single oral dose of 10 mg test and reference nisoldipine tablets were given to 24 male healthy volunteers in an open randomized 2?2 latin square design.The plasma concentrations of nisoldipine at different time points were determined by LC-MS and the pharmacokinetic parameters of the two kinds of tablets were computed and their bioequiavailability was evaluated.RESULTS:The main pharmacokinetic parameters of the test vs.reference formulations of nisoldipine in 24 healthy volunteers were as follows:Cmax(2.94?2.78)ng?mL-1 vs.(3.22?2.16)ng?mL-1,tmax(1.70?1.00)h vs.(1.40?1.00)h,t1/2(6.81?4.11)h vs.(5.55?2.35)h,AUC0～24(10.60?7.70)ng?h?mL-1 vs.(9.90?6.76)ng?h?mL-1,AUC0～∞(11.30?7.90)ng?h?mL-1 vs.(10.20?7.00)ng?h?mL-1.The relative bioavailability of domestic nisoldipine tablets was(110.3?30.8)%.CONCLUSION:The reference preparation and the test preparation of nisoldipine tablets were proved to be bioequivalent.

Objective To compare the vascularization of collagen scaffolds with or without growth factors and their efficacy on cardiac function in postinfarcted rats underwent surgical ventricular restoration.Methods Collagen scaffolds were activated with 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride chemistry (EDC) as control or continually covalently immobilized with vascular endothelial growth factor (VEGF) and VEGF + basic fibrohlast growth factor (bFGF) as experimental groups.Adult SD male rats underwent left anterior descending artery (LAD) ligation to generate transmural myocardial infarction(MI).Four weeks later,by echocardiography,rats with moderate scar size(25％-35％ akinetic area of freedom wall of left ventricle) were screened out,assigned into 3 groups randomly and received the surgical ventricular restocation (SVR).Then,cardiac function was measured by echocardiography at 1w,2w and 4w after patch implantation.At endpoint of study (4w after patch implantation),the rats were sacrificed and the hearts were harvested.Vascularization of patch were determined by capillary density (evidenced by vWFⅧ staining) or mature vessel density (evidenced by SMA staining) respectively.Results The general mortality of the animal model is 15％ (6/40).A significant improvement of cardiac function was observed in all animals at 1 w after patch implantation but that was better preserved in both cytokine-conjugated groups 4w later (control group vs.VEGF group,P ＜ 0.05,control group vs.VEGF + bFGF group,P ＜ 0.01).More capillaries were present in patch with growth factors (P ＜0.05),while significant functional vessel formation was observed only in VEGF + bFGF group (P ＜0.01 vs.control or VEGF group).Additionally,we identified a positive correlation between heart function and mature vessel density (P =0.0297,r2 =0.998).Conclusion The mechanical property of collagen scaffold can be effectively improved by EDC,the growth factors immobilized in scaffold were in favor of vascularization of patch,which may facilitate the preservation of cardiac function posterior to SVR.

Objective To observe the clinical efficacy of the combination of modification ofChaihu Jia Longgu MuliDecoction with psychological intervention in the treatment of post tumor depression.MethodsTotally 122 cases of post tumor depression were divided into treatment group and control group by simple numeration table random method, with 61 cases in each group. The treatment group was given modification ofChaihu Jia Longgu Muli Decoction orally, at the same time psychological intervention was given. The control group was given escitalopram oxalate tablets for 6 weeks. HAMD scale scores of the two groups were observed before and after treatment to evaluate the clinical efficacy. Changes in life quality of two groups were scored with SF-36 scale. The adverse reactions were also observed.ResultsAfter treatment, the HAMD score of treatment group was lower than control group (P<0.05). The total effective rate was 88.52% (54/61) in the treatment group and 72.13% (44/61) in the control group, with statistical significance (P<0.05). The scores of life quality of treatment group were higher than control group (P<0.05), and the incidence of adverse reactions was lower than control group (P<0.05).Conclusion Combination of modification ofChaihu Jia Longgu MuliDecoction with psychological intervention in the treatment of post tumor depression can significantly improve the depressive state and life quality of the patients with post tumor depression, which is better than the control group, without significant adverse reactions.

OBJECTIVETo study the effect of 3'-methoxy puerarin on cerebral ischemic glutamic acid, aspartic acid, taurine and gamma-aminobutyric acid inhibitory of rats and investigate the protective mechanisms of cerebral ischemia-reperfusion.

METHODUsing middle cerebral artery occlusion rat model, to collect extracellular fluid in rat striatal amino acid neurotransmitters by brain microdialysis and HPLC techniques with fluorescence detection before and after 3'-methoxy puerarin treatment four kinds of amino acids changes.

RESULT3'-methoxy puerarin reduced concentrations of excitatory amino acid (EAA) Asp and Glu, while Tau and GABA inhibitory amino acids were significantly reduced.

CONCLUSION3'-methoxy puerarin reduce ischemia-induced brain EAA toxicity against EAA neurotoxicity, regulate the brain neurotransmitter amino acid content, improve the excitatory and inhibitory amino acid balance is one of the mechanisms that to improve and protect the important acute cerebral infarction in rat brain nuclei.

Animals ; Brain Ischemia ; drug therapy ; metabolism ; Excitatory Amino Acids ; metabolism ; Female ; Isoflavones ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism

OBJECTIVETo observe the effect of 3'-methoxy puerarin on cerebral infarction volume and free radical change of focal cerebral ischemia-reperfusion injury in rats and discuss the protective effect of 3'-methoxy puerarin on the cerebral ischemic/ reperfusion injury.

METHODThe thread method was used to induce middle cerebral artery embolization, to establish the focal cerebral ischemia-reperfusion model. Rats were divided into five groups: the sham and model group, the two-dose group (5, 10 mg x kg(-1) x d(-1)) of 3'-methoxy puerarin and nimodipine group (5 mg x kg(-1) x d(-1)). The behavior changes and volume of cerebral infarction were observed, and the leves of SOD and the content of MDA were measured.

RESULT3'-methoxy puerarin could significantly improve the symptoms of neurological deficit and reduce the infarct volume, and increased SOD activity and reduced the content of MDA of cortex in cerebral ischemia-reperfusion injury rat, the action of 10 mg x kg(-1) of 3'-methoxy puerarin is more remarkable.

CONCLUSION3'-methoxy puerarin has protective effect on focal cerebral ischemia-reperfusion injury in rat.

Animals ; Brain Ischemia ; drug therapy ; prevention & control ; Disease Models, Animal ; Female ; Humans ; Isoflavones ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; prevention & control

Objective To investigate the feasibility of multiple model parameters of intravoxel incoherent motion (IVIM) in differential diagnosis of cervical carcinoma and its pathological types.Methods IVIM images of 33 patients with cervical cancer (cervical cancer group) and 30 patients with normal cervix (normal group) were retrospectively analyzed.The monoexponential model parameters (ADC-stand),biexponential model parameters (ADC-slow,ADC-fast,f) and stretched-exponential model values (distributed diffusion coefficient [DDC],α) were measured,respectively.Then the parameters were compared among the two groups,as well as among different pathological types and different pathological grades of cervical cancer.The thresholds and diagnostic efficiency of the parameter values were evaluated with ROC curve.Results ADC-stand,ADC-slow,f,DDC and α values of cervical cancer group were lower than those of normal group (all P＜0.05).The area under the ROC curve of ADC-stand,ADC-slow,DDC,f and a values in diagnosis of cervical cancer was 0.93,0.94,0.96,0.94 and 0.93 (all P＜0.05),and the diagnostic thresholds were 1.03 × 10-3 mm2/s,0.99 × 10-3mm2/s,30.50％,1.21 × 10-3 mm2/s and 0.699,respectively.ADC-stand,ADC-slow and DDC values in cervical squamous cell carcinoma patients were lower than those of cervical adenocarcinoma patients (all P＜0.05).The area under the ROC curve of ADC-stand,ADC-slow and DDC values in differential diagnosis of cervical squamous cell carcinoma and cervical adenocarcinoma was 0.98,0.91 and 0.98 (all P＜0.05),the diagnostic thresholds were 1.11 × 10-3 mm2/s,0.81×10-3 mm2/s and 0.98 × 10-3 mm2/s,respectively.There was no significant difference of the parameters among high,moderate,low differentiation of cervical squamous cell carcinoma.Conclusion Multiple model parameters of IVIM can quantitatively reflect the histological features of cervical cancer.

Objective: To understand the sanitation status of teaching environment of schools in Beijing, and to provide basis for school environmental improvement through monitoring it. Methods: In 2019, 661 primary and secondary schools were selected according to the coverage rate of 50% of all schools. Two classrooms were randomly selected from each school for testing, 1 322 classrooms were monitored. The testing contents included per capita area of the classroom, rate of correct desks-chairs adjusting for school height, blackboard size, reflection ratio of blackboard,illumination, carbon dioxide and noise. Results: The qualified rate of noise(92.3%), per capita area(86.5%), blackboard size (85.6%) and illumination uniformity of table top (83.4%) were higher than 80%, while the qualified rate of other indexes were lower than 80%. In 2019, the qualified rate of blackboard size, blackboard average illuminance and blackboard illuminance uniformity were higher than 2018 year(85.6%, 52.7%, 36.2%; 81.9%, 42.7%, 31.7%)(χ2=10.97, 7.80, 5.90, P<0.05), while the noise (92.3%) was lower than 2018 year(98.3%)(χ2=70.82, P<0.05). Both classroom and blackboard, the average illuminance and evenness of the desk and blackboard installed with LED light were higher than those installed with fluorescent lights. Conclusion Teaching environment monitoring in Beijing is not optimistic. It is necessary to strengthen the promotion and evaluation of standards,and the classroom environment needs to be further improved.

Objective:To summarize the experience of treatment for chronic pancreatitis by analyzing the clinical information of 10 533 patients with chronic pancreatitis admitted to First Affiliated Hospital of Naval Medical University (Changhai Hospital) in the past 28 years.Methods:Clinical data including the age, sex, place of birth, admission time, admission age, admission department, discharge time, hospitalization times and treatment methods of chronic pancreatitis patients admitted to Changhai Hospital from January 1995 to February 2022 were analyzed retrospectively. The changes of chronic pancreatitis patients′ admission, demographic characteristics and treatment mode were summarized.Results:A total of 10 533 patients were analyzed, including 7 443 males (70.66%) and 3 090 females (29.34%), and male to female ratio was 2.41∶1. The average age of admission was (45.7±15.0) years. In terms of geographical distribution, East China was the largest, followed by North China and Northwest China. 10 533 patients were admitted for 19 920 times, and there were 18 156 times (91.14%) in gastroenterology department and 1 452 times (7.29%) in general surgery department. Patients in gastroenterology department were admitted for (1.88±1.45) times and the average length of hospitalization was (10.33±5.63) days. A total of 14 134 endoscopic retrograde cholangiopancreatography [(1.45±1.41) times per patient] were performed among 8 022 patients, and 13 882 pancreatic extracorporeal shock wave lithotripsy [(2.22±0.36) times per patient] were performed among 6 629 patients. In general surgery department, patients were admitted for (1.03±0.16) times and the average length of hospitalization was (14.90±9.00) days. 1 242 patients underwent surgical treatment. The ratio of endoscopic therapy to surgery increased from 0.12∶1 in 1995 to 15.72∶1 in 2021.Conclusions:The study shows that chronic pancreatitis was more common in middle-aged males in China, and the treatment modes of chronic pancreatitis in Changhai Hospital had changed from surgery to endoscopic therapy.